This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term objective of this proposed project is to determine functions of TGF-beta in cancer survellience and intervention and to improve the effectiveness of a novel laser immunotherapy by reducing TGF-beta levels in teh tumor cells. Laser immunotherapy was developed by the PIs, using a near-infrared laser, indocyanine green (ICG, a light-absorbing dye), and blycated chitosan (GC, a proprietary immunoadjuvant) for treatment of metastatic tumors. Our previous studies using laser immunotherapy have shown extremely promising outcomes in the treatment of late-stage, metastatic tumors, both in animal models and in human trials for melanoma and breast tumors. TGF-beta has been shown to be a crucial cytokine in cancer surveillance and intervention. It is hypothesized that reducing TGF-beta levels in tumor microenvironment could significantly enhance the outcomes of laser immunotherapy in treating metastatic tumors through the enhanced anti-tumor immune responses. In this study, we plan to achieve the following specific aims: (1) to reduce TGF-beta levels in DMBA-4 tumor cells for in vitro ain in vivo studies;(2) to determine the effects of TGF-beta reduction on laser immunotherapy treatment of metastatic tumors in rats;(3) to investigate the effects of TGF-beta reducatino on immune cells in the tumor microenvironment. This one-year collaborative grant will allow an initial investigation of the functions of TGF-beta and the mechanism of laser immunotherapy, paving he way for a large-scale, in-depth future study for TGF-beta associated tumor treatment modalities.